Hydrochloric Acid → 4-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-2,5-dimethylphenyl)-1-(4-methoxybenzyl)piperidin-2-one

HRID 536372Notes

Reaction equation

HRID 536372 reaction equation
[NH2:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[C:11](=[O:24])[CH2:10]2)=[C:4]([CH3:25])[CH:3]=1.Cl[C:27]1[N:32]=[C:31]([NH:33][C:34]2[CH:38]=[C:37]([CH3:39])[NH:36][N:35]=2)[C:30]([Cl:40])=[CH:29][N:28]=1.Cl.C([O-])(O)=O.[Na+]>CC(O)C>[Cl:40][C:30]1[C:31]([NH:33][C:34]2[CH:38]=[C:37]([CH3:39])[NH:36][N:35]=2)=[N:32][C:27]([NH:1][C:2]2[C:7]([CH3:8])=[CH:6][C:5]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][C:16]4[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=4)[C:11](=[O:24])[CH2:10]3)=[C:4]([CH3:25])[CH:3]=2)=[N:28][CH:29]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 114022722,5-Dichloro-N-(5-methyl-1H-pyrazol-3-yl)-4-pyrimidinamineHCID 671555764-(4-Amino-2,5-dimethylphenyl)-1-(4-methoxybenzyl)piperidin-2-one

Product 1

HCID 671555134-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-2,5-dimethylphenyl)-1-(4-methoxybenzyl)piperidin-2-one

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
130 °C

Procedure

To a mixture of 4-(4-amino-2,5-dimethylphenyl)-1-(4-methoxybenzyl)piperidin-2-one (23 mg, 0.094 mmol) and 2,5-dichloro-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine (29 mg, 0.086 mmol) in iPrOH (1 mL) was added HCl (60 uL, 4N in dioxane). The reaction vessel was then sealed and heated to 130° C. for 4 hr. After cooling to room temperature, the mixture was treated with saturated NaHCO3 aqueous solution (3 mL) and extracted with EtOAc (3×4 mL). The organic layers were combined and concentrated. The residue was purified by flash column chromatography (silica gel, gradient 0˜10% MeOH/CH2Cl2) to provide 4-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-2,5-dimethylphenyl)-1-(4-methoxybenzyl)piperidin-2-one. ESMS m/z 546.2 (M+H+).

Workup

  1. customThe reaction vessel was then sealed
  2. temperatureAfter cooling to room temperature
  3. extractionextracted with EtOAc (3×4 mL)
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography (silica gel, gradient 0˜10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-7b539f28872a43c5b488d36d8ac21d9c
Source dataset
uspto-grants-2014_10
Patent number
US08859574B2

Reaction notes

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